Congenital anomalies are the second leading cause of perinatal mortality in the United States after premature birth. Advances in imaging techniques have allowed the in utero detection of many anatomical defects with ultrasound. The goal of this project is to improve the diagnosis and treatment of fetal disease and congenital anomalies. The Perinatology Research Branch has initiated a series of projects to improve the detection of congenital anomalies and assess fetal growth and development with the use of three-dimensional ultrasound. A substantial effort has been invested in the development of techniques to improve the prenatal diagnosis of congenital heart disease since this is the leading cause of death among fetuses with congenital anomalies. The findings of this year include the following: 1. Digital casts of the great vessels and venous return to the heart using four-dimensional ultrasound: Investigators at the Perinatology Research Branch described a technique for reconstruction of the great vessels and venous return to the heart using four-dimensional ultrasonography with spatiotemporal image correlation (STIC), and inversion mode or B-flow imaging. Four-dimensional reconstruction of cardiovascular structures using these techniques allowed the visualization of ?digital casts? similar to the silicone rubber casts of the cardiovascular system that can be obtained during postmortem examinations. Spatial relationships between the outflow tracts, the connections of the great arteries to the ventricular chambers, and the connections between the venous system and atrial chambers could be clearly observed. The technique was applied to the diagnosis of coarctation of the aorta, transposition of the great arteries, double outlet right ventricle, pulmonary stenosis, pulmonary atresia and interruption of the inferior vena cava with azygous or hemiazygous continuation. In addition to improved visualization of the outflow tracts and venous return to the heart, the application of inversion mode to volume datasets of the four-chamber view allowed sharper delineation of the cardiac contours, atrioventricular valves and ventricular septal defects when compared to two-dimensional ultrasound. Three-dimensional ultrasound with inversion mode was also used for the reconstruction of fluid-filled structures such as the stomach, the ventricular system of the brain, and dilated ureters and renal pelvis in cases of urinary tract obstruction. 2. Individualized growth assessment of normal fetuses using three-dimensional ultrasound: This study introduced a new soft tissue parameter that can be evaluated by three-dimensional ultrasound -fractional arm volume (AVol) - for longitudinal assessment of fetal growth. Individualized growth standards based on Rossavik models were developed using AVol, mid arm circumference (ArmC), and humeral diaphysis length (HDL). Twenty-two fetuses were prospectively studied by two- and three-dimensional ultrasound. Second-trimester models were constructed from the linear slopes of growth curves before 28 weeks of gestation and normal third-trimester trajectories were predicted for each parameter. The Rossavik functions fit all parameter trajectories extremely well (R(2)=95.7%-99.4%) and the mean percent deviations between observed and predicted third-trimester HDL, ArmC, and AVol measurements were -0.1% +/- 2.9%, 0.5% +/- 4.6%, and 0.4% +/- 8.5%, respectively. The study demonstrated that individualized growth assessment can be performed by volumetric measurements of the fetal arm and that third trimester fetal arm growth can be accurately predicted. AVol may allow early detection and improved monitoring of soft tissue abnormalities that occur in fetuses with growth disorders. 3. Prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes: The Branch examined the clinical significance of dense aggregates of particular matter in the proximity of the cervical canal ? amniotic fluid ?sludge? - an ultrasound finding that is frequently observed in patients with preterm labor and intact membranes. The prevalence of amniotic fluid ?sludge? was determined in 84 patients with preterm labor and intact membranes and 298 uncomplicated pregnancies at term. The frequency of microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks were compared between the two groups. The prevalence of amniotic fluid 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. The rate of spontaneous preterm delivery was higher in patients with amniotic fluid 'sludge'. Patients with amniotic fluid ?sludge? had a higher frequency of positive amniotic fluid cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] and, in addition, their neonates were admitted to the NICU [64.3% (9/14) vs. 12.9% (8/62), P < 0.01] or died more often [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those without amniotic fluid 'sludge'.